Identification and characterization of variants of tick anticoagulant peptide with increased inhibitory potency toward human factor Xa

The inhibitory potency of tick anticoagulant peptide (TAP), a specific and potent inhibitor of a central enzyme in the blood clotting cascade for human factor Xa (fXa), can be significantly enhanced to 2.5 to 4-folds by site-directed mutagenesis of Tyr-1 to Trp (Y1W) and Asp-10 to Arg (D10R) respectively. Amino acid substitutions of Tyr-1 by Phe showed no effect on the inhibitory potency of TAP toward the human fXa.